Abstract
The outcome for patients with refractory or relapsed acute lymphoblastic leukemia (ALL) treated with conventional therapy is poor. Immunoconjugates present a novel approach and have recently been shown to have efficacy in this setting. Combotox is a mixture of two ricin-conjugated monoclonal antibodies (RFB4 and HD37) directed against CD19 and CD22, respectively, and has shown activity in pediatric and adult ALL. We created a murine xenograft model of advanced ALL using the NALM/6 cell line to explore whether the combination of Combotox with the cytotoxic agent cytarabine (Ara-C) results in better outcomes. In our model the combination of both low- and high-dose Combotox and Ara-C resulted in significantly longer median survival. Sequential administration of Ara-C and Combotox, however, was shown to be superior to concurrent administration. These findings have led to a phase I clinical trial exploring this combination in adults with relapsed or refractory B-lineage ALL (ClinicalTrials.gov identifier NCT01408160).
Original language | English (US) |
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Pages (from-to) | 1999-2003 |
Number of pages | 5 |
Journal | Leukemia and Lymphoma |
Volume | 53 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2012 |
Keywords
- Acute lymphoblastic
- Animal model
- Cytarabine
- Immunoconjugate
- Leukemia
- Mouse
- NOD
- Ricin
ASJC Scopus subject areas
- Hematology
- Oncology
- Cancer Research